Effects of Nylidrin, Isoproterenol and Phenoxybenzamine on Dogs Subjected to Hemorrhagic Shock

Abstract

The effects of beta-adrenergic receptor stimulants (nylidrin and isoproterenol) on the hemorrhagic shock state of anesthetized dogs were measured and compared to those of phenoxybenzamine to determine the therapeutic effectiveness of the combined cardiac stimulatory and peripheral vasodilatory actions of the former drugs. Anesthetized dogs were subjected to 3 hours of hypovolemia followed by the return of the shed blood. Nylidrin, isoproterenol (continuous infusion), and phenoxybenzamine were administered 1 hour after bleeding the animals and heart rate, arterial blood pressure, venous hematocrit, coronary blood flow, cardiac output, ventricular contractility, and survival rates were measured. Nylidrin and isoproterenol afforded significant protection against shock deaths, whereas phenoxybenzamine did not increase survival over control values. Mild to moderate intestinal hemorrhage and distention were noted in the isoproterenol- and phenoxybenzamine-treated animals, but not in the nylidrin-treated animals. Phenoxybenzamine gradually decreased the arterial blood pressure and additional quantities of blood had to be infused to maintain cardiac output and blood pressure. Ventricular contractile force progressively decreased in the phenoxybenzamine-treated animals, whereas isoproterenol and nylidrin enhanced the force of ventricular contractions. In the presence of existing hypotension, isoproterenol and nylidrin maintained cardiac output. These agents deserve further consideration as potentially useful therapeutic agents in the management of shock states.